Understanding Vascular Endothelial Cell Behavior Using a Mechanical Strain Gradient Generated by an Electromagnetic Stretching Device

Abstract

Cardiovascular diseases cause an estimated 17.9 million deaths globally each year (World Health Organization). Endothelial cells that line the vasculature and the endocardium are subjected to cyclic mechanical stretch. Deviation from physiological stretch can alter the endothelial function, having the risk of atherosclerosis and myocardial infarction. To understand the mechanical stretch effects, cell culture platforms that provide mechanical stretch have been developed. However, most of them have fixed strain and frequency, sometime not in the pathophysiological range. We thus developed a novel, electromagnetically driven, uniaxial stretching device, where cells were grown on a flexible polydimethylsiloxane (PDMS) membrane mounted onto a 3-D printed track. The strain of the membrane was readily controlled by tailoring the track design and the frequency was determined by electromagnetic actuation. Furthermore, the mechanical strain gradient was generated on a PDMS membrane with a tapered thickness. This strain gradient, ranging from 1.5% to 40%, covered both physiological and pathological vascular stretch ranges. When human vascular endothelial cells were subjected to the cyclic stretch, the cells exhibited strain-dependent cell and nuclear orientation and elongation perpendicular to the stretching direction, compared to the random cell and nuclear orientation under the static condition. However, the overstretching led to deviation from the aforementioned orientation and elongation, and impaired the tight junctions, leading to a leaky endothelium. This novel, versatile, cost-effective, pathophysiologically relevant stretching device provides a useful platform for advancement of vascular disease research and treatment.